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Biomedical subjects

B Barber

Publications and source records attributed to B Barber.

At least 19 recordsLinked to original sources

Assembly of MHC class I molecules analyzed in vitro.

Recent evidence suggests that peptide ligands take part in the assembly of class I molecules in living cells. We now describe a simple system for studying class I assembly in vitro. Detergent extracts of the mutant cells RMA-S and .174, in which class I assembly does not occur spontaneously, will support assembly in vitro when specific peptides are added. Peptides stabilize a conformational change in the class I heavy chain and association with beta 2-microglobulin, at concentrations approximately 100-fold lower than required in "peptide feeding" experiments with whole cells. We show that peptides bind class I molecules during assembly and demonstrate that the conformational change induced in the heavy chain is influenced by the concentrations of both peptide and beta 2-microglobulin.

Amino Acid Sequence

Genetic aspects of ion transport systems in hypertension.

Environmental factors, genetic polymorphism and differences in experimental design have been the main impediments to evaluating the evidence for a genetic association between cell membrane cation transport abnormalities and human essential or genetic hypertension. The present paper reviews the results obtained in the Milan hypertensive rat (MHS) and in its corresponding normotensive strain (MNS) in order to illustrate our approach to defining the role of cation transport abnormality in a particular type of genetic hypertension. Kidney cross-transplantation between the strains showed that hypertension is transplanted along with the kidney. Proximal tubular cell volume and sodium content were lower in MHS rats while sodium transport across the brush border membrane vesicles of MHS rats was faster. Erythrocytes of MHS rats have a smaller volume, faster Na,K cotransport and a lower Km for internal sodium compared with MNS rats. The faster cotransport is also present in renal cells of the ascending limb and in vascular muscle cells. Moreover, these erythrocyte abnormalities are genetically associated in F2 hybrids and are primarily determined in the stem cells. These differences in ion transport between MHS and MNS rats are not present when studied in erythrocyte inside-out vesicles, which are deprived of membrane skeletal proteins, suggesting that a molecular abnormality underlies the functional one. We have identified a point mutation of one of these cytoskeletal membrane protein adducin genes in MHS rats. At present we are evaluating the possibility that mutation of the adducin gene in MHS rats might account for the differences in ion transport and, therefore, in blood pressure between the two strains.

Animals

Rationale for a community strategy in the field of information and communications technologies applied to health care.

The challenge for Europe in the field of information and communications technologies applied to health care is that of addressing positively the problem of the widening gap between the expectations of the citizens of the type of care that can be made available and the limited resources to provide that care. If the expectations of the population are to be fulfilled, it will be necessary to find innovative ways of delivering health services and to do it more efficiently than has yet been the case. Advanced information and communications technologies will be important tools for Member States to achieve the levels of efficiency required. Based on the results of the Community AIM Exploratory Action, further collaborative work is required at EEC level to create an Integrated Health Information Environment (IHE) allowing essentially for integration, modularity and security.

Europe

Angiotensin restores atrial natriuretic factor-induced decrease of baroreceptor sensitivity in normotensive rats, but not in spontaneously hypertensive rats.

The effect of atrial natriuretic factor (ANF) on baroreflex sensitivity was determined in unanesthetized normotensive (Wistar-Kyoto, WKY) or spontaneously hypertensive rats (SHR) during acute hypertensive stimuli (phenylephrine) or hypotensive stimuli (sodium nitroprusside). The i.v. dose of rat ANF [( Ser99,Tyr126]ANF) was 50 ng/min per rat, sufficient to decrease mean arterial blood pressure (ABP) by about 6 mmHg (1 mmHg = 133.3 Pa) in WKY. SHR showed no change in ABP with this ANF dose. During a control infusion of physiological saline, the mean heart rate (HR) response to increases in ABP was -1.30 +/- 0.27 beats/min (bpm)/mmHg in WKY and -0.37 +/- 0.22 in SHR (p less than 0.05). These values were not affected significantly by ANF. However, ANF blunted chronotropic responses to ABP decreases. The control values of the delta HR/delta ABP slope in WKY and SHR were -2.34 +/- 0.57 and -2.01 +/- 0.37 bpm/mmHg, respectively. In the presence of ANF, the slope changed to -0.36 +/- 0.43 (i.e., bradycardia in response to hypotension) in WKY and to +0.20 +/- 0.21 in SHR (p less than 0.005 for the difference from control for both). This ANF-induced loss of baroreflex sensitivity was reversed in WKY by the addition of angiotensin I (sufficient to increase ABP by 5 mmHg in control rats). Angiotensin did not restore baroreflex sensitivity in ANF-infused SHR, and ANF had no effect on the ABP increase caused by angiotensin in either group. The data suggest that ANF does not act on baroreceptor structures directly, but inhibits mechanisms involved in efferent sympathetic activation. Parasympathetic responses do not appear to be compromised.

Angiotensin I

Calcium dependence of rhythmic contractions of the Oryzias latipes blastoderm.

1. The blastoderm of the Oryzias latipes (medaka, Teleostei) embryo begins to contract rhythmically, about once per min at 25 degrees C, during epiboly. When the blastoderm was mechanically detached from the rest of the egg, it contracted into a pear-shaped ball and also continued to contract rhythmically. 2. The optimal [Ca2+] for the rhythmic contractions was approximately 1 mM. 3. The contractions stopped in media containing La3+, Ni2+, Mn2+, Co2+ or Ba2+. 4. A number of organic calcium antagonists--cinnarizine, D600, diltiazem, nifedipine, TMB-8 and verapamil--had no apparent effect on the contractions. However, the contractions were inhibited by papaverine, caffeine, and a mixture of TMB-8 and verapamil. 5. The contractions stopped in a medium containing 25 mM K+ or cytochalasin D. 6. We conclude that microfilaments cause the contractions, that each rhythmic contraction is preceded or accompanied by an increase in cytoplasmic free [Ca2+], and that Ca2+ enters the cytoplasm from both an extracellular and an intracellular pool.

1-Methyl-3-isobutylxanthine

Dose of human menopausal gonadotropin influences the outcome of an in vitro fertilization program.

This study compares outcomes of in vitro fertilization (IVF) in two groups of 57 patients when either 2 (group 1) or 3 (group 2) ampules of human menopausal gonadotropin (hMG) were administered daily. Treatment began on day 3 of the cycle and was discontinued when at least 2 follicles attained diameters greater than or equal to 1.5 cm. Human chorionic gonadotropin (hCG) was given either 24 or 48 hours after the last dose of hMG. Although serum estradiol levels were lower in group 1, the average number of oocytes retrieved (3.2 versus 2.9), fertilized (1.9 versus 2.0), and cleaved (1.7 versus 1.8) per completed cycle did not differ between groups 1 and 2. Likewise, the number of oocytes that fertilized abnormally was similar in both groups (0.5 versus 0.3/cycle). However, the number of atretic oocytes (0.03 versus 0.5/cycle) and the percent of oocytes recovered from the cul-de-sac (0 versus 7.2%) were significantly (P less than 0.05) lower in group 1. In group 1, administration of hCG 48 hours after the last dose of hMG was associated with a higher number of cleaving embryos (2.1 versus 1.5/cycle) and a higher pregnancy rate (34.8 versus 14.7%; P less than 0.05) when compared with injection at 24 hours. In group 2, the interval between hMG and hCG did not influence these results. Together, the associations between fewer oocytes that were atretic or recovered from the cul-de-sac, and a trend toward a higher pregnancy rate, suggest that follicular recruitment with 2 ampules of hMG is more appropriate than 3 ampules in an IVF program.

Chorionic Gonadotropin

On the determination of isozyme levels in preparations containing cytoplasmic and mitochondrial aspartate aminotransferase.

A spectrophotometric assay has been developed for the determination of the content of each isozyme of aspartate transaminase (L-aspartate:2-oxoglutarate aminotransferase, EC 2.6.1.1) in physiological fluids or tissue extracts. The methods relies on the ability of adipate, at low pH and ionic strength to inhibit the cytoplasmic isozyme but not the one from mitochondria. Two assays are necessary, one at pH 8.0 which measures the content of both isozymes and another at low pH which measures primarily the amount of mitochondrial isozyme. Results obtained by this simple procedure match those in which each isozyme is inhibited by its antibody. The validity of the results obtained by the new method was tested at different ratios of cytoplasmic:mitochondrial isozyme and with tissue extracts. Since the amounts of each isozyme determined by radial immunodiffusion match those values gathered by following enzymatic activity, it is concluded that the quantity of each isozyme obtained from its respective catalytic activity must represent the total protein content of each isozyme in a given sample.

Animals